The LINC00519/hsa-miR-22-3p/MECOM Axis Accelerates Intrahepatic Cholangiocarcinoma Progression through PI3K/AKT Signaling.

Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. LINC00519 plays a prominent role in the progression of numerous cancers. To explore the molecular mechanism of LINC00519 in ICC, the expressions of LINC00519, hsa-miR-22-3p, and MECOM in ICC were assessed using the ENCORI database and qRT-PCR. The biological functions of LINC00519 in ICC were examined using a clone formation experiment, Transwell analysis, flow cytometry, and Western blot. Meanwhile, the mechanism of LINC00519 in ICC was determined by a dual-luciferase reporter assay. Results showed that LINC00519 and MECOM were highly expressed in ICC, whereas hsa-miR-22-3p was decreased. Functionally, silencing LINC00519 weakened ICC cell proliferation and migration and induced cell apoptosis. Also, LINC00519 knockdown repressed the PI3K/AKT (protein kinase B) pathway. Mechanistically, LINC00519 acted as a competitive endogenous RNA to target MECOM by sponging hsa-miR-22-3p. Meanwhile, rescue assays further proved that low LINC00519 expression restrained ICC cell proliferation and migration and accelerated apoptosis through the PI3K/AKT pathway by miR-22-3p/MECOM. In conclusion, this research revealed a novel LINC00519/hsa-miR-22-3p/MECOM regulatory axis and PI3K/AKT pathway that modulated ICC progression. IMPLICATIONS: This study deepens the understanding of the noncoding RNA regulatory network in ICC and provides potential targets for the diagnosis and targeted therapy of ICC.